<b>Purpose:</b> To establish a novel panel of cancer-specific methylated genes for cancer detection and prognostic stratification of early-stage non-small cell lung cancer (NSCLC).<b>Experimental Design:</b> Identification of differentially methylated regions (DMR) was performed with bumphunter on "The Cancer Genome Atlas (TCGA)" dataset, and clinical utility was assessed using quantitative methylation-specific PCR assay in multiple sets of primary NSCLC and body fluids that included serum, pleural effusion, and ascites samples.<b>Results:</b> A methylation panel of 6 genes (<i>CDO1, HOXA9, AJAP1, PTGDR, UNCX</i>, and <i>MARCH11</i>) was selected from TCGA dataset.